Active components, such as drugs or pharmaceuticals, may be prepared in a tablet form to allow for accurate and consistent dosing. However, this form of preparing and dispensing medications has many disadvantages including that a large proportion of adjuvants that must be added to obtain a size able to be handled, that a larger medication form requires additional storage space, and that dispensing includes counting the tablets which has a tendency for inaccuracy. In addition, many persons, estimated to be as much as 28% of the population, have difficulty swallowing tablets. While tablets may be broken into smaller pieces or even crushed as a means of overcoming swallowing difficulties, this is not a suitable solution for many tablet or pill forms. For example, crushing or destroying the tablet or pill form to facilitate ingestion, alone or in admixture with food, may also destroy the controlled release properties.
As an alternative to tablets and pills, films may be used to carry active components such as drugs, pharmaceuticals, and the like. However, historically films and the process of making drug delivery systems therefrom have suffered from a number of unfavorable characteristics that have not allowed them to be used in practice.
Films that incorporate a pharmaceutically active component are disclosed in expired U.S. Pat. No. 4,136,145 to Fuchs, et al. (“Fuchs”). These films may be formed into a sheet, dried and then cut into individual doses. The Fuchs disclosure alleges the fabrication of a uniform film, which includes the combination of water-soluble polymers, surfactants, flavors, sweeteners, plasticizers and drugs. These allegedly flexible films are disclosed as being useful for oral, topical or enteral use. Examples of specific uses disclosed by Fuchs include application of the films to mucosal membrane areas of the body, including the mouth, rectal, vaginal, nasal and ear areas. Examination of films made in accordance with the process disclosed in Fuchs, however, reveals that such films suffer from the aggregation or conglomeration of particles, i.e., self-aggregation, making them inherently non-uniform.
Certain methods of manufacturing film products involve mixing all of the components together, and then dispensing or extruding the mixture into a film. However, when the pharmaceutically active component or other components that react with water-based solvents come into contact with the water-based film solution, they may react in undesirable ways, such as by crystallizing or becoming amorphous. This is especially true when water-active components are in contact with the water-based solution for an extended period of time. When the components crystallize or clump together, the resulting mixture becomes less uniform, as higher dosages of the grouped together components settle in various areas of the mixture, and also becomes more difficult to prepare films.
When large dosages are involved, even a small change in the dimensions of the film may lead to a large difference in the amount of active present per film. If a sheet of film (also known as a “web”) includes areas with lower dosages of active, it is possible that portions of the film may be substantially devoid of any active. Since sheets of film are usually cut into unit doses, certain doses, particularly those falling in the middle of the sheet, may therefore be devoid of or contain an insufficient amount of active for the recommended treatment. Failure to achieve a high degree of accuracy with respect to the amount of active component in the cut film can be harmful to the patient. For this reason, dosage forms formed by processes such as Fuchs may not meet the stringent standards of governmental or regulatory agencies, such as the U.S. Federal Drug Administration (“FDA”), relating to the variation of active in dosage forms. Currently, as required by various world regulatory authorities, dosage forms may not vary more than 10% in the amount of active present. When applied to dosage units based on films, this virtually mandates that uniformity in the film be present.
The benefits of preparing a film that is substantially uniform in composition, without adding additional components are numerous. In addition to the obvious cost-savings through using minimal materials, there is a greater percentage of films that are pharmaceutically acceptable. Thus, less film will be deemed “unacceptable”, resulting in less wasted active component. Further, with a more uniform distribution of active, there can be provided a lesser amount of active provided to the mixture overall. When there is a non-uniform distribution of active, more active must be added to the mixture to compensate for those portions that are non-uniform.
Systems for mixing and dispensing urethanes, epoxies, silicones and the like for sealing, potting, and bonding are known. These systems provide a means for rapidly forcing a chemical reaction by mixing, followed by dispensing of the material as the reaction proceeds. In these cases, if the reacted mixture stays in the mixing compartment too long, it will harden, making dispensing difficult, if not impossible. However, until now, these systems have not been used for quickly mixing and dispensing for the purpose of avoiding a chemical reaction.
Therefore, there is a need for methods of manufacture and compositions of film products, which use a minimal number of materials or components, and which allow the various components to mix and dispense rapidly and dry, reducing the amount of time that the water-active components are in contact with the water-based solution.